The objectives of this proposal are: to determine the abilities of mammalian cells in vitro to recover from drug-induced potentially lethal and sublethal damage; To determine the relationships between recovery and the cell cycle stage during sensitivity, and to the drug effects on cell progression kinetics and division; To define the requirements for recovery from drug damage, and to inhibit recovery either through the use of dose fractionation of multiple drug combinations; To determine the reasons for the differential drug survival responses observed between dividing and nondividing cells; To describe the effects of drug treatments on recruitment or inhibition of reentry of nondividing cells into the cell cycle; To determine changes in drug sensitivities of previously treated clones of cells; To characterize all of these phenomena on dividing, nondividing and synchronized cells and on populations of cells in which dividing and nondividing cells have been mixed to produce experimentally derived growth fractions; To use the data obtained from these experimental systems to plan relevant, rational, and effective drug protocols for the treatment of solid tumors. BIBLIOGRAPHIC REFERENCES: Barranco, S.C., B.R. Haenelt and W.E. Bolton. Cell Cycle Time Determinations Based on Liquid Scintillation Counting of 3HTdR Labeled Mitotic Cells. Cell and Tissue Kinetics, in press, March, 1977. Barranco, S.C. and D.R. Flournoy. Cell Killing, Kinetics, and Recovery Respones Induced by 1,2:5,6-Dianhydrogalactitol in Dividing and Nondividing Cells in Vitro. J. National Cancer Institute, in press, 1977.